PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies
BackgroundIndication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), resul...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949933/full |
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| author | Tahm Spitznagel Laurenz S. Matter Yves L. Kaufmann Jakob Nilsson Seraina von Moos Thomas Schachtner |
| author_facet | Tahm Spitznagel Laurenz S. Matter Yves L. Kaufmann Jakob Nilsson Seraina von Moos Thomas Schachtner |
| author_sort | Tahm Spitznagel |
| collection | DOAJ |
| description | BackgroundIndication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes.MethodsWe analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm.ResultsGroup NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086).ConclusionsPIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies. |
| first_indexed | 2024-04-13T13:10:22Z |
| format | Article |
| id | doaj.art-1014f8d7fb694b3cb9dc1481efa85d3b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T13:10:22Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1014f8d7fb694b3cb9dc1481efa85d3b2022-12-22T02:45:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.949933949933PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsiesTahm Spitznagel0Laurenz S. Matter1Yves L. Kaufmann2Jakob Nilsson3Seraina von Moos4Thomas Schachtner5Division of Nephrology, University Hospital of Zurich (USZ), Zurich, SwitzerlandDivision of Nephrology, University Hospital of Zurich (USZ), Zurich, SwitzerlandDivision of Nephrology, University Hospital of Zurich (USZ), Zurich, SwitzerlandDivision of Immunology, University Hospital of Zurich (USZ), Zurich, SwitzerlandDivision of Nephrology, University Hospital of Zurich (USZ), Zurich, SwitzerlandDivision of Nephrology, University Hospital of Zurich (USZ), Zurich, SwitzerlandBackgroundIndication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes.MethodsWe analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm.ResultsGroup NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086).ConclusionsPIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.949933/fullHLA epitope mismatchTCMRABMRborderline rejectionkidney allograft biopsy |
| spellingShingle | Tahm Spitznagel Laurenz S. Matter Yves L. Kaufmann Jakob Nilsson Seraina von Moos Thomas Schachtner PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies Frontiers in Immunology HLA epitope mismatch TCMR ABMR borderline rejection kidney allograft biopsy |
| title | PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies |
| title_full | PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies |
| title_fullStr | PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies |
| title_full_unstemmed | PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies |
| title_short | PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies |
| title_sort | pirche ii scores prove useful as a predictive biomarker among kidney transplant recipients with rejection an analysis of indication and follow up biopsies |
| topic | HLA epitope mismatch TCMR ABMR borderline rejection kidney allograft biopsy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949933/full |
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